NET-inducing ability of Cutibacterium acnes clinical isolates is associated with pathogenicity in acne vulgaris

Background Cutibacterium acnes strains vary in virulence and inflammatory potential in acne vulgaris, but the role of the bacterial ability to induce neutrophil extracellular traps (NETs) in acne is unclear. Methods We collected 18 clinical isolates from acne patients and healthy controls and analyzed the correlation between C. acnes NET-inducing ability and bacterial virulence involved in acne vulgaris pathogenicity. Results Eighteen clinical strains were classified into 17 IA1 and 1 IA2 phylotypes. Supernatants from five acne-associated strains exhibited marked NET-inducing activity, which was strongly correlated with cytokine production and reactive oxygen species generation. The NET-inducing capacity of supernatants was also positively correlated with bacterial hemolytic activity against human erythrocytes and biofilm formation. In a mouse ear model, NET-inducing strains caused more-severe lesions than NET-noninducing strains. Whole-genome sequencing revealed substantial genetic variation between the NET-inducing strain (C009) and NET-noninducing ATCC strain. Conclusion These findings suggest that NET induction represents one of virulence-associated phenotypes linked to pathogenicity in C. acnes-induced acne vulgaris.